New 4-methoxy-naphthalene derivatives as promisor antifungal agents for paracoccidioidomycosis treatment.

AIM: Novel 4-methoxy-naphthalene derivatives were synthesized based on hits structures in order to evaluate the antifungal activity against Paracoccidioides spp.

METHODS

Antifungal activity of compounds was evaluated against P. brasiliensis and most promising compounds 2 and 3 were tested against eight clinically important fungal species.

RESULTS

Compound 3 was the more active compound with MIC 8 to 32 μg.ml-1 for Paracoccidioides spp without toxicity monkey kidney and murine macrophagecells. Carbohydrazide 3 showed good synergistic antifungal activity with amphotericin B against P. brasiliensis specie. Titration assay of carbohydrazide 3 with PbHSD enzyme demonstrates the binding ligand-protein. Molecular dynamics simulations show that ligand 3 let the PbHSD protein more stable.

CONCLUSION

New carbohydrazide 3 is an attractive lead for drug development to treat paracoccidioidomycoses.